Immunological responsiveness to bacterial infections may play an important role in conditioning the ability of burn patients to resist and combat the frequently occurring bacteremia and septicemia of "burn disease." The immune response genes of the Major Histocompatibility Complex (MHC) (Ir genes) appear to be directly involved in immunological responsiveness, and therefore genetic factors may play an important role in the degree of mortality after severe thermal injury. The mortality rates of ten different strains of mice with distinct MHC genetic backgrounds were followed after 40 percent full-thickness skin burns. Significant variations of host susceptibility or resistance to the lethal effects of thermal injury were observed. Strains Fisher, Long Evans, and ACI appeared to be particularly susceptible and 80-100 percent of the animals succumbed in the first 6 days. On the other hand, strains Wistar-Furth and Brown Norwegian showed significant resistance to thermal injury, and approximately 60 percent survived for long periods after injury. Intermediate resistance was found in strains Osborne-Mendel, Lewis and Buffalo, where approximately 30 percent of the animals survived. All data were statistically analyzed by non-linear analysis of the least squares fitting and the above discrimination between low, intermediate and high mortality rates among the strains was found significant. The results indicate that resistance or susceptibility to the lethal effects of thermal injury may correlate with the genetic makeup of the different strains, and more particularly with the products of the Major Histocompatibility genes in rats.